Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein interactions.
Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein interactions.
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DOI：
10.1016/j.molcel.2012.02.012
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发表时间：
2012-04-27
期刊：
影响因子：
16
通讯作者：
Cho, Wonhwa
中科院分区：
文献类型：
--
作者：
Chen, Yong;Sheng, Ren;Kaellberg, Morten;Silkov, Antonina;Tun, Moe P.;Bhardwaj, Nitin;Kurilova, Svetlana;Hall, Randy A.;Honig, Barry;Lu, Hui;Cho, Wonhwa
新出现的证据表明，膜脂质调节蛋白质网络直接与蛋白质相互作用域（PID）。作为一个试点研究，以确定和功能注释的脂质结合PID的基因组规模，我们进行了实验和计算研究PDZ域。对70个PDZ结构域的表征表明，40%具有亚微摩尔膜亲和力。使用从这些数据建立的计算模型，我们预测了20个物种的2000 PDZ域的膜结合特性。对26个PDZ结构域进行了实验验证。我们还细分脂质结合PDZ域分为三类膜和蛋白质结合位点之间的相互作用的基础上。对于不同类型的PDZ结构域，脂质结合通过不同的机制调节它们的蛋白质相互作用。PDZ结构域蛋白rhophilin2的功能研究表明，所有类别的脂质结合PDZ结构域作为真正的双特异性模块调节蛋白质在生理条件下的膜相互作用。
Emerging evidence indicates that membrane lipids regulate protein networking by directly interacting with protein-interaction domains (PIDs). As a pilot study to identify and functionally annodate lipid-binding PIDs on a genomic scale, we performed experimental and computational studies of PDZ domains. Characterization of 70 PDZ domains showed that 40% had submicromolar membrane affinity. Using a computational model built from these data, we predicted the membrane binding properties of 2000 PDZ domains from 20 species. The accuracy of the prediction was experimentally validated for 26 PDZ domains. We also subdivided lipid-binding PDZ domains into three classes based on the interplay between membrane and protein binding sites. For different classes of PDZ domains, lipid binding regulates their protein interactions by different mechanisms. Functional studies of a PDZ domain protein, rhophilin2 suggest that all classes of lipid binding PDZ domains serve as genuine dual-specificity modules regulating protein interactions at the membrane under physiological conditions.
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